Neurodegeneration refers to the progressive loss of structure or function of neurons, including death of neurons. This deterioration gradually causes a loss of cognitive abilities such as memory and decision making. Neurodegeneration is a key aspect of a large number of diseases encompassed under the term, “neurodegenerative diseases.” Although hundreds of different neurodegenerative disorders exist, research and attention have primarily focused on amyotrophic lateral sclerosis (“ALS”), Parkinson disease (“PD”), Huntington disease (“HD”), and Alzheimer disease (“AD”). All of these conditions lead to progressive brain damage and neurodegeneration. The causes of these neurodegenerative diseases are essentially unknown, and even when they have been identified, the mechanisms by which they initiate the disease remain speculative. At the present time, these neurodegenerative diseases are incurable.
Huntington's disease (“HD”) has emerged as a model for studying neurodegenerative disease pathogenesis. HD is a hereditary brain disorder that affects muscle coordination and leads to mental decline and behavioral symptoms. The disease is caused by an autosomal dominant mutation in either of an individual's two copies of a gene called Huntingtin. This means a child of an affected person typically has a 50% chance of inheriting the disease. While there are medications that may help treat symptoms of the disease, researchers are still actively looking for a treatment that can delay the onset or slow the progression of HD. Currently, about 30,000 people in the U.S. have HD and up to 200,000 people are at risk.
Recently, dietary supplementation with creatine has been of interest for treating neurodegenerative diseases due to its anti-inflammatory and mitochondrial stabilizing effects. For example, there has been favorable rodent data to support ultra-high doses of creatine supplementation in food as a means to prevent or reduce neurodegeneration in HD mouse models. In addition, there have been some clinical trials involving the use of creatine supplementation in treating neurodegenerative disorders in HD patients. However in these clinical trials, dosages of 30 grams or more of creatine monohydrate per day were needed in order to obtain favorable results. In other words, relatively large doses of creatine monohydrate must be consumed for effective use. As toxicity for any consumable is typically related to the dose (i.e., the amount taken) and the length of the exposure, large doses of creatine monohydrate, such as those indicated, result in increased toxicity and an increased risk of undesired side effects. In addition, due to the large dosages of creatine monohydrate, patients are often required to consume the creatine monohydrate through multiple administrations per day. For example, a 30 gram daily dose of creatine monohydrate would typically mean 3-4 doses of 8-10 grams per day. As it is often difficult for patients to adhere to multiple administrations per day, this leads to compliance issues in many patients.
Accordingly, there remains a need for a more improved form of creatine with improved solubility and bioavailability characteristics that can be consumed in smaller dosage forms while also retaining the desired biological effects of creatine supplementation for treatment of neurodegeneration.